This proposed research is concerned with the molecular mechanisms involved in the control of virus gene expression at transcriptional, post-transcriptional and translational levels. We proceed with the bacteriophage T7 - Escherichia coli system as a simple virus-host model system and aim to obtain through understanding of virus development which is applicable to other viruses including animal viruses and tumor viruses. T7 genes and corresponding mRNAs and proteins have been subject to extensive genetic and biochemical studies and it is now well established that the early genes are transcribed by the host RNA polymerase and the late genes are transcribed by the T7-coded RNA polymerase which is one of the T7 early gene products. However, this unique transcriptional control by two different RNA polymerases is not sufficient to explain the early-late switch in T7 phage gene expression. Our specific research aims are directed toward the following areas: 1. T7 early mRNA is chemically stable but functionally unstable. Unique structural features (secondary structure) and the processing of the RNA will be investigated. 2. Possible translational discrimination between T7 early mRNA in T7 infected cells will be investigated with a special attention to the F facto-mediated restriction of T7 in "male" strains of E. coli. Our data suggests that there is no translational discrimination. 3. "Host shut-off" function of T7 which inactivates the host E. coli RNA polymerase will be elucidated. An inhibitor protein of the host enzyme has been isolated and purified from T7 infected cells. Genetic studies on the T7 gene coding for this protein and biochemical studies on the mode of inhibition by this protein will be performed. BIBLIOGRAPHIC REFERENCES: Yamada, Y. and Nakada, D. Early to late switch in bacteriophage T7 development: No translational discrimination between T7 early messenger RNA and late messenger RNA. J. Mol. Biol., 100, 35-45 (1976). Yamada, Y. and Nakada, D. Translation of T7 RNA in vitro without cleavage by RNase III. J. Virol., 18, 1155-1159 (1976).